Method and apparatus for coating balloon catheters

ABSTRACT

A coating apparatus for coating the balloon portion of a balloon catheter is described. The coating apparatus includes a rotatable member in which the catheter portion of the balloon catheter is mounted and fixed, and which causes rotation of the balloon catheter. The apparatus also includes a support member in which the distal tip of the catheter is inserted and free to rotate; and a spray nozzle directing sprayed material on the balloon surface. The inventive configuration of the coating apparatus allows the balloon catheter to be rotated along its axis with insubstantial or no wobble, which significantly improves the quality of the coating applied to the surface of the balloon.

CROSS-REFERENCE TO RELATED APPLICATION

The present non-provisional patent application claims priority under 35U.S.C. §119(e) from U.S. Provisional Patent Application having Ser. No.61/188,929, filed on Aug. 14, 2008, and titled METHOD AND APPARATUS FORCOATING BALLOON CATHETERS, wherein the entirety of said provisionalpatent application is incorporated herein by reference.

FIELD OF THE INVENTION

The invention relates to a spray coating apparatus and methods fordisposing a coating material on a medical device surface.

BACKGROUND OF THE INVENTION

Functional improvements to implantable or insertable medical devices canbe achieved by coating the surface of the device. For example, a coatingformed on the surface of the device can provide improved lubricity,improved biocompatibility, or drug delivery properties to the surface.In turn, this can improve movement of the device in the body, extend thefunctional life of the device, or treat a medical condition near thesite of implantation. However, various challenges exist for the designand use of coating apparatus designed to provide coatings to medicaldevices.

Traditional coating methods, such as dip coating, are often undesirableas they may result in flawed coatings that could compromise the functionof the device or present problems during use. These methods can alsoresult in coating inaccuracies, which can be manifested in variableamounts of the coated material being deposited on the surface of thedevice. When a drug is included in the coating material, it is oftennecessary to deliver precise amounts of the agent to the surface of thedevice to ensure that a subject receiving the coated device receives aproper dose of the agent. It has been difficult to achieve a greatdegree of accuracy using traditional coating methods and machines.

As another challenge, implantable or insertable medical devices aretypically small and often have unusual, complex configurations. As ageneral matter, the handing of these devices in an appropriate mannerduring a coating procedure is often challenging.

Spray coating techniques have been used to apply coating material tovarious devices, including medical devices. See, for example, U.S. Pat.Nos. 6,562,136, 7,077,910, 7,125,577, and 7,192,484. In some cases, acoating process involves repetitively applying a coating material to afixtured device in order to achieve a target quantity and quality ofcoated material. Devices are often manipulated between the applicationsof the coating material and dried to a certain extent before thesemanipulations are performed. It is often difficult to fixture andmanipulate the devices so they receive a desired coating of material. Itis also often difficult to prevent the coating apparatus and method fromintroducing defects into the formed coating.

One type of insertable medical device is a balloon catheter. Ballooncatheter constructions are well known in the art and are described invarious documents, for example, U.S. Pat. Nos. 4,195,637, 5,041,089,5,087,246, 5,318,587, 5,382,234, 5,571,089, 5,776,101, 5,807,331,5,882,336, 6,394,995, 6,517,515, 6,623,504, 6,896,842, and 7,163,523.Balloon catheters generally include four portions, the balloon, cathetershaft, guidewire, and manifold. A balloon catheter generally includes anelongated catheter shaft with an inflatable balloon attached to a distalsection of the catheter shaft. At a proximal end of the catheter shaft,there is typically a manifold. At the manifold end, placement of thecatheter can be facilitated using a guidewire. Guidewires are small andmaneuverable when inserted into an artery. Once the guidewire is movedto the target location, the catheter with balloon portion is then fedover the guidewire until the balloon reaches the target location in thevessel. The balloon is typically inserted into the arterial lumen of apatient and advanced through the lumen in an unexpanded state. Theballoon is then inflated when the catheter reaches target site resultingin application of mechanical force sufficient to cause vessel dilation.The balloon is typically inflated using a fluid, which is injectedthrough an inflation port. The manifold can control the fluidintroduction within shaft for expansion of the balloon. The mechanics offluid transfer and introduction within balloons vary according to thespecific design of the catheter, and are well know in the art.

Applicants have found that the complex design of a balloon catheter hasmade the balloon portion of the catheter difficult to coat. Accordingly,Applicants have provided new equipment and methods useful for overcomingthe problems associated with the spray coating of medical devices, suchas balloon catheters.

SUMMARY

The invention generally relates to an apparatus and methods for coatingan implantable or insertable medical device. In embodiments of theinvention, the methods and apparatus are directed towards coating aninsertable medical device having an expandable elastic portion, such asa balloon catheter.

In one aspect, the invention provides a coating apparatus for rotatablycoating an insertable or implantable medical device, such as a ballooncatheter. The coating apparatus includes a rotatable member in which acatheter portion of a balloon catheter can be fixed and rotated. Therotatable member has an elongate shape with a distal end, a proximalend, and a central axis. The central axis of the rotatable member isaccessible, and the catheter portion can be fixed in the rotatablemember along the central axis so the catheter axis is aligned with thecentral axis. The coating apparatus also includes a support memberhaving an aperture that is aligned with the central axis of therotatable member. The support member is capable of holding the distaltip of the balloon catheter, but allows for rotation of the ballooncatheter when the catheter portion is fixed and rotated by the rotatablemember. The distal end of the rotatable member is separated from thesupport member by a gap. The gap has a length sufficient to accommodatethe length of the balloon portion of the balloon catheter. The coatingapparatus also includes a spray nozzle capable of delivering a spray ofcoating material in the gap between the distal end of the rotatablemember and the support member. When a balloon catheter is mounted inposition, the spray nozzle can deliver a spray of coating material tothe balloon surface.

The invention also provides a method for spray coating a material on thesurface of a portion of a balloon catheter. The method includes a stepof providing a balloon catheter comprising a catheter portion having acatheter axis, a balloon portion, and a distal tip. The balloon catheteris then mounted in a coating apparatus having a rotatable member, asupport member, and a spray nozzle. In the step of mounting, a part ofthe catheter portion is fixed by the rotatable member, so that thecatheter axis is aligned with the central axis of the rotatable member.The step of mounting also includes inserting the distal tip of theballoon catheter in the support member so that it is held, but free torotate in place. With the catheter portion fixed, and distal tipsupported, the balloon catheter is straightened and rotatable along thecentral axis. In another step, the balloon catheter is rotated about itscentral axis. In another step, a coating of material is applied to thesurface of the balloon from a spray nozzle.

Generally, the distance between the distal end of the rotatable memberand the support member is the same or greater than the distance of theballoon portion as measured along the catheter axis.

In some aspects, the support member comprises a grommet in which thedistal tip of the catheter is held and rotatable in. In some aspects,the support member is rotatable.

In some aspects the apparatus further includes a drive mechanism thatcan drive rotation of the rotatable member. Preferably, the drivemechanism is mechanically coupled to the rotatable member. For example,the drive mechanism can be coupled to the proximal end of the rotatablemember.

In some aspects, the coating nozzle is movable in a direction along thecentral axis of the apparatus, which is in line with the central axis ofthe rotatable member. Accordingly, in one preferred aspect of thecoating process, the spray nozzle is moved along the length of theballoon portion of the balloon catheter. In some cases the steps ofdisposing the coating material and moving the spray nozzle are performedsimultaneously.

In some aspects the apparatus further includes a balloon inflationdevice (e.g., Indeflator™). The balloon inflation device can be used forinsertion or removal of gas from the balloon portion of the ballooncatheter. Accordingly, in some aspects, the method includes a step ofinflating the balloon portion of the balloon catheter. In some aspects,the method includes applying a coating of material to the surface of theballoon when the balloon is inflated. The tip of the spray nozzle can bepositioned at an appropriate distance from the balloon surface toprovide a desired application of coating material on the surface.

The balloon catheter can be rotated by the rotatable member in acontinuous or an intermittent manner. In some aspects, the ballooncatheter is continuously rotated while a spray of coating material isdeposited on the balloon surface. For intermittent rotation, therotatable member can be coupled to a drive mechanism having an indexingfunction.

The invention provides advantages for the coating of medical devices, inparticular balloon catheters. For example, the apparatus improves aballoon catheter coating process because the spraying of the entirecircumference of the balloon surface can be carried out with rotationalmovement, and during the rotation there is little or no deviation in thedistance between the balloon surface and the tip of the spray nozzle. Assuch, the coating apparatus and method can provide precise positioningand uniform rotation of the balloon catheter with respect to the sprayhead. This is achieve because the rotatable member and support memberare arranged and are able to secure the balloon catheter in such a waythat the axis of the balloon catheter remains straight during therotational movement, thereby preventing unsteady or wobbly rotation ofthe balloon. This ultimately provides a more uniform coating becausethere is minimal variance of the distance between the tip of the coatingnozzle and the surface of the balloon being coated while the ballooncatheter is being rotated.

In addition, the apparatus is advantageous in that it can allow forrapid loading and removal of pre-inflated balloon catheters withoutcoiling or kinking the of the catheter portions.

In addition, the apparatus is advantageous in that it can protect thecatheter from extraneous coating flux.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a standard balloon catheter.

FIG. 2 is an illustration of a cross section of one embodiment of thecoating apparatus with a mounted balloon catheter.

FIG. 3 is an illustration of an embodiment of the rotatable member.

FIG. 4 is another illustration of an embodiment of the rotatable member.

FIGS. 5a, 5b, and 5c are illustrations of cross sections of therotatable member as viewed from its distal end.

FIG. 6 is an illustration of the distal portion of the rotatable member,the support member, and a mounted balloon catheter.

FIG. 7 is an illustration of an embodiment of the coating apparatusshowing the rotatable member, the support member, and a spray nozzleattached to a movable track.

DETAILED DESCRIPTION OF THE INVENTION

The embodiments of the present invention described herein are notintended to be exhaustive or to limit the invention to the precise formsdisclosed in the following detailed description. Rather, the embodimentsare chosen and described so that others skilled in the art canappreciate and understand the principles and practices of the presentinvention.

All publications and patents mentioned herein are hereby incorporated byreference. The publications and patents disclosed herein are providedsolely for their disclosure. Nothing herein is to be construed as anadmission that the inventors are not entitled to antedate anypublication and/or patent, including any publication and/or patent citedherein.

One aspect of the present invention relates to an apparatus for coatinga balloon catheter. The apparatus includes a rotatable member, a supportmember, and a spray nozzle. The rotatable member and support member arearranged along the same axis of rotation (herein referred to as the“central axis”) and are separated by a gap. The gap between therotatable member and support member is large enough to accommodate aballoon portion (lengthwise) of a balloon catheter. The rotatable membercan also secure or fix the catheter portion of the balloon catheter inplace so that it can be rotated about its axis (i.e., the catheteraxis), which is also coincident with the central axis of the device. Therotatable member can include a cavity that runs along the central axisin which the catheter portion of the balloon catheter can be placed andthen secured. The rotatable member can have a cylindrical or tubularshape. The rotatable member can also be mechanically associated with adrive mechanism that can be actuated to promote rotational movement ofthe rotatable member.

The support member can hold the distal end (tip) of the balloon catheterin place so that the balloon catheter is essentially straight from itsproximal end to its distal end. This can ensure that rotation of theballoon catheter can be performed with essentially little or no wobble,which, in turn, improves the spray coating process.

The spray nozzle is configured to produce a spray of a coating materialthat is directed towards the gap between the rotatable member andsupport member. When the catheter portion of the balloon catheter isfixed by the rotatable member and the distal tip is held by the supportmember, and when the spray nozzle is actuated, the balloon surface canbe coated with coating material. The coating process can be carried outwhile the balloon catheter is rotated, which can cause the coatingmaterial to be deposited about the periphery of the balloon. Also, thespray nozzle can be movable in a direction along the central axis of thedevice. The spray nozzle can be moved in proximal to distal, and/ordistal to proximal directions along the central axis when the spraynozzle is actuated to provide a coating to the surface of the balloon.

In some modes of practice, a coating process can involve applying thecoating material multiple times (i.e., multiple applications of acoating material) on the surface of the balloon while the ballooncatheter is being rotated. For example, with movement of the spraynozzle, the coating material can be applied from the spray nozzle fromthe distal end of the balloon portion to its proximal end (or from thedistal to proximal end) on one portion of the balloon surface. Thedevice can be rotated and then the coating material can be applied againalong another portion of the balloon surface. These applications ofcoating material can be repeated to provide a coating on the balloonsurface with a desired amount of coating material.

In some modes of practice, the same or overlapping portions of thedevice are coated multiple times in order to produce a balloon surfacehaving a desired quality or quantity of coating material. For example,after a portion of the balloon surface is coated with a firstapplication of a coating material, the balloon catheter is then rotatedto place the surface in position for a subsequent application of acoating material. Rotation of the balloon catheter can be continuous orintermittent.

The coating apparatus and/or method of the invention can be used toprepare coatings described in commonly assigned U.S. patent applicationSer. No. 12/383,751, filed on Mar. 27, 2009 (Arps et al.).

In order to describe the invention in greater detail, reference to thefollowing illustrations are made. The illustrations are not intended tolimit the scope of the invention in any way but are to demonstrate someof the various embodiments of the coating apparatus and its features.

First, in order to explain the details of the coating apparatus andmethod, reference is made to a standard balloon catheter, as shown inFIG. 1. A standard balloon catheter includes a catheter body 10(tubing/shaft) that extends most or all of the length (L) of the device,a tip 11 at the distal end of the device, a balloon portion 12 which canbe inflated, an inflation aperture 13 for the balloon, and an inflationport 14 at the proximal (user) end. Although the catheter body runs mostof the length of the device, for purposes of discussion, the “catheterportion” of the device refers to that between the point where theinflation port meets the catheter body and the proximal end of theballoon.

The catheter body is typically flexible so that it can navigate throughthe arterial system when introduced into a subject. A more rigid portion15 of the catheter is proximal to the inflation port 14. The catheterbody (from proximal to distal end) can be straightened so the catheterfollows a linear path. The catheter body can be held in a straightenedconfiguration using the coating apparatus, as described herein. When thecatheter body is straightened along a linear path, the catheter can havean axis “catheter axis” CA about which the catheter can be rotated whenmounted in the coating apparatus of the invention. The length (L) ofballoon catheters can vary; standard lengths being in the range of about50 cm to about 150 cm.

In one embodiment, the coating apparatus includes a rotatable member, asupport member, and a spray nozzle. FIG. 2 shows the apparatus 20 with amounted catheter 21. The coating apparatus 20 according to the inventioncan include a housing 22 on which the coating process can be performed.Mounted to a portion of the housing is the rotatable member 23 (a distalportion of the rotatable member 23 is shown), which can be used to fixat least a part of the catheter portion of the balloon catheter near theballoon portion and rotate the balloon catheter about the central axis.The rotatable member 23 is shown having a cylindrical shape and istapered at its distal end 24.

The rotatable member 23 is attached to rotatable member mounting units26 a and 26 b that support the rotatable member in a horizontalposition. The rotatable member mounting units are attached at theirbases to the housing 22.

As shown in FIG. 2, the rotatable member 23 has a central axis that runsparallel to the catheter portion 21 of the balloon catheter when thecatheter is fixed in place. The rotatable member 23 includes a centralportion which encompasses the central axis of the rotatable member andthat can accommodate the catheter portion 21 of the balloon catheter.When the catheter portion 21 is fixed in placed within the centralportion of the rotatable member 23, as shown in FIG. 2, the axis of thecatheter is aligned with the central axis of the rotatable member 23.Since the catheter axis is aligned with the central axis, upon rotationthere is no, or negligible, wobble of the balloon catheter.

The apparatus 20 also includes a distal tip support member 27, (alsoreferred to as “support member” herein) which is shown in as a part of asupport member mounting unit 28. The support member 27 can support thedistal end (tip) of the balloon catheter 25 and allow it to rotatefreely when the balloon catheter is rotated. The support member mountingunit 28 is shown attached at it base to the housing 22. Optionally, thedistal tip support member 27 can rotate freely in the support membermounting unit 28.

The apparatus 20 also includes a spray mechanism, the spray nozzle 29 ofwhich is shown. The spray nozzle 29 is able to produce a spray SP ofcoating material that is directed at the surface of the balloon portion30 of the balloon catheter when mounted in the apparatus.

The rotatable member is able to fix the catheter portion of the ballooncatheter in place and rotate it for the spray coating process. Since,generally, the catheter portion of the balloon catheter is long, therotatable member can also be long to accommodate the catheter portion.For example, the rotatable member can have a length similar to that ofthe overall length of the balloon catheter.

An illustration of an entire rotatable member 33 is shown in FIG. 3.

The rotatable member can be of any suitable size and shape to fix thecatheter portion in place and cause rotational movement of the ballooncatheter. In many aspects, the rotatable member has an elongated shape.The elongated shape can include a cylindrical shape (viewed in crosssection), such as shown in FIGS. 2 and 3, providing the outer surface ofthe rotatable member 33 with a curved surface. However, other shapesthat provide the rotatable member with one or more flat outer surfacesare contemplated. Viewed as a cross-section of the rotatable member, theother shapes may be polygonal (hexagonal, octagonal, etc.). In someaspects, the rotatable member may also have one or more different shapesalong its length. For example, as shown in FIG. 3, the rotatable member33 has a cylindrical shape towards the distal end of the apparatus, anda shape that is partially cylindrical (such as half a cylinder) towardsthe proximal end of the apparatus.

A rotatable member 33 with a fully cylindrical-shaped distal end canprotect the catheter portion of the balloon catheter (proximal to theballoon portion) from any extraneous coating flux during the spraycoating process. Further, and as a general matter, a fully cylindricallyshaped distal end can facilitate the fixation of at least the part ofthe catheter portion near the balloon so the catheter body is alignedwith the central axis of the rotatable member.

The distal end 34 of rotatable member can also be tapered. As shown inFIG. 3, the distal end has a conical shape.

In many aspects, the rotatable member has a cross-sectional diameter inthe range of about 2 cm to about 10 cm. In an exemplary design, thecross-sectional diameter is about 4 cm. In many aspects, the rotatablemember has a length from the proximal end to the distal end in the rangeof about 50 cm to about 200 cm; in an exemplary design, the length isabout 100 cm.

As shown in FIG. 3, the rotatable member 33 is attached to rotatablemember mounting units 36 a, 36 b, and 36 c that hold the rotatablemember in a horizontal position and that are attached to the housing 32.

The proximal portion of the coating apparatus is shown in greater detailin FIG. 4. FIG. 4 illustrates a drive mechanism 45 that is directlyconnected to the rotatable member 43. The drive mechanism can includeany suitable motor (such as a standard DC motor) to drive movement ofthe rotatable member.

Alternatively, the drive mechanism can be indirectly mechanicallyassociated with the rotatable member. For example, one or morecomponents (e.g., a drive shaft, belt, etc.) can be located between thedrive mechanism and the rotatable member to translate movement and causerotation of the rotatable member.

The drive mechanism can optionally have an indexing function that allowsfor intermittent rotation of the rotatable member. Intermittent rotationcan be useful during the spray coating processes wherein partialrotation of the device is performed after a spray coating of material isapplied to the device. An indexing function of the roller drivemechanism will be described in greater detail below.

The rotatable member can also include a central portion thataccommodates the catheter portion of the balloon catheter. The rotatablemember can have a design so its central portion is accessible and thecatheter portion can be placed in alignment with the central axis of,and fixed within, the rotatable member.

In some aspects, at least the distal portion of the rotatable member isconfigured so the central portion can be accessed. In one aspect, atleast the distal portion of the rotatable member is split along itslength (from proximal to distal ends). For example, the rotatable membercan have a split cylindrical configuration, as shown in FIG. 5a (asviewed from proximal or distal ends). One half 51 of the split cylindercan be separated from the other half 52 to expose the central portion.For example, in one arrangement, the two half cylinders can be hingedalong one side to allow for opening and closing of the rotatable member.

In some aspects, at least the distal portion of the rotatable memberincludes a cavity that can accommodate the catheter portion of theballoon catheter. The cavity can be of a suitable shape andconfiguration to accommodate the catheter portion of the ballooncatheter in the rotatable member. Generally, along at least a part ofthe length of the rotatable member, the cavity is elongate and has acurved inner surface, sufficient to accommodate the catheter portion.For example, referring to FIG. 5c , as viewed from the proximal ordistal end of the rotatable member, the cavity 53 can have a circularshape (when the split cylindrical halves are placed together); FIG. 5bshows one half 54 of a split cylinder with a semicircular cavity 55. Insome cases, the cavity forms an opening at the distal end of therotatable member having a diameter in the range of about 0.1 cm to about1.0 cm in diameter, with 0.3 cm being a typical diameter. In many casesthe cavity can have a shape that fits the shape of the outside of thecatheter portion of the balloon catheter.

The rotatable member can be formed of any suitable durable material, forexample, stainless steel, polyoxymethylene (POM) (e.g., Delrin),acrylonitrile butadiene styrene (ABS), polyvinyl chloride (PVC),polycarbonates, polysulfones, or glass.

Referring back to FIG. 1, the coating apparatus 20 according to theinvention includes a support member 27. The support member 27 cansupport the distal end 25 of the balloon catheter (i.e., the tip of theballoon end of the device) so the catheter can be maintained in a linearconfiguration and the balloon catheter can be rotated about its axiswhen rotation of the device is commenced. Essentially, the distal tip ofthe device is held in the support member, but is allowed to rotatefreely. The support member can include a low friction material thatcontacts the surface of the distal end 25 of the balloon catheter, thelow friction material facilitating the overall rotation of the ballooncatheter.

The center of the support member 27 is aligned with the central axis ofthe rotatable member 23.

As shown in greater detail in FIG. 6, in some designs of the coatingapparatus, the support member 67 is mounted in or on a support membermounting unit 68 that holds the support member 67 in a horizontalposition. FIG. 6 also shows that a proximal part of the catheter portionfixed in the rotatable member 63. The balloon portion 60 thereforebecomes positioned between the distal end of the rotatable member 63 andthe support member 67.

As shown in FIG. 6, the support member 67 has a circular shape and isheld within a recess in the support member unit 68. As shown in FIG. 6,the tip of the balloon catheter is held in the center of the supportmember 67. The support member 67 can be in the form of a grommet oreyelet. The center of the support member 67 can have an orifice oraperture into which the distal end (tip) 65 of the balloon catheter isplaced. For example, the grommet can have a center that is configured toreceive the distal end 65 of the catheter and hold it in place duringrotation of the catheter. The orifice or aperture preferably has adiameter in the range of about 0.1 cm to about 2.0 cm, with an exemplarydiameter being about 0.3 cm.

Optionally, the support member can be rotatable along with the ballooncatheter. In this case, the support member could be a second rotatablemember of the device, with the part of the apparatus that fixes thecatheter portion being a first rotatable member. If the support memberis rotatable it can also be configured to secure the distal end of theballoon catheter. For example, the support member can have a clampingfeature so that when the distal end of the balloon catheter is insertedin the center of the support member, it cannot easily be pulled out ofplace. The clamping feature may be provided by forming the supportmember out of an elastomeric material into which the distal end of theballoon cathetercan be inserted and held. For example, the supportmember can include a rubber ring with a hole in the center, the holebeing smaller than the diameter of the distal end of the ballooncatheter. When the distal end of the balloon catheteris inserted intothe hole in the ring, pressure is applied to the outer surface of thedistal end of the balloon catheter, which holds the distal end in place.This secures the distal end (tip) of the catheter and prevents it frommoving in a proximal to distal or distal to proximal directions when theballoon catheter is mounted in the apparatus. Rotation of the supportmember 67 can be facilitated by including bearings, or the like, aroundthe member to minimize any resistance to rotational movement.Optionally, the rotation of the support member 67 can be facilitated bymechanically coupling the support member to a drive mechanism. If thesupport member is coupled to a drive mechanism, it can be the same drivemechanism that drives rotation of the rotatable member.

Optionally, the coating apparatus can include more than one pair of therotatable member and the support member. Having multiple pairs of therotatable and support members can be useful to increase processthroughput if it desired to provide coatings to a plurality of ballooncatheters. Multiple rotatable members can be aligned on the apparatus sotheir central axes are parallel to each other. Multiple support memberscan be arranged so they are aligned with the central axes of eachrespective rotatable member. Balloon catheters can be loaded into eachpair of rotatable and support members. Other configurations of multiplerotatable and support members are contemplated, such as those whereinpairs of multiple rotatable and support members are movable on thesurface of the coating apparatus, such as in a track system, to bring apair of members into a coating zone for the application of a coating.

If the apparatus includes more than one pair of rotatable and supportmembers, one or both member of the pair can be mechanically associatedwith a common drive member. For example, a common drive member can bemechanically connected to multiple rotatable members, and can causerotation of all of the rotatable members when actuated.

A single coating nozzle can be used for the coating of multiple ballooncatheters. Function and movement of the spray coating nozzle in aspectsof the invention having rotatable and support members are described ingreater detail herein.

The coating apparatus also includes a spray nozzle configured to producea spray of coating material which can be deposited on the balloonsurface of the balloon catheter when mounted in the apparatus for aspray coating process. As shown in FIG. 2, the spray nozzle 29 isarranged on the coating apparatus to delivery a spray of coatingmaterial SP between the distal end of the rotatable member 24, and theproximal face of the support member 27. When the balloon catheter ismounted in the apparatus, the nozzle can deliver a spray of coatingmaterial to the balloon surface. The area in which the spray of materialis applied can be referred to as the “coating zone.” The coating zone isan area where the spray coating process takes place and in which spraynozzle is movable.

Referring to FIG. 7, the spray nozzle 79 can be mounted on an arm 72 sothat the spray nozzle 79 is appropriately positioned relative to therotatable member 73 and the support member 77. The arm 72 can beadjustable to provide a desired distance between the balloon surface(when the balloon catheter is mounted on the coating apparatus) and thetip of the spray nozzle 79, from which the spray of coating materialemanates. (Without the balloon catheter mounted in the apparatus, thepositioning of the spray nozzle can also be described as the distancebetween the tip of the spray nozzle and the imaginary line thatrepresents the central axis of the first and support member.)

In many aspects, the tip of the spray nozzle is positioned close to thecentral axis of the coating apparatus. For example, the distance betweenthe tip of the spray nozzle and the central axis is in the range ofabout, 5 mm to about 25 mm, more specifically in the range of about 5 mmto about 10 mm, or in one exemplary embodiment about 8 mm.

In many aspects of the invention, the spray nozzle is movable. Forexample, as shown in FIG. 7, the spray nozzle 79 is movable indirections parallel to the central axis as shown by arrows 71 and 71′.In one arrangement, the spray nozzle 79 is mounted on an arm 72, and aportion of the arm 72 is within a track 74 in a mounting unit 75 whichallows the arm 72 to moves in a direction along the central axis. Thetrack 74 can include a motorized unit that controls the movement of thearm 72, and thus movement of the spray nozzle 79 in relation to theballoon catheter that is mounted in position. A track motor (not shown)can drive the movement of the arm 72, via a belt, chain, pulley, cord,or gear arrangement.

As such, the spray nozzle can be movable to provide a coating of spraymaterial along the length of the surface of the balloon providing a“stripe” of coating material deposited along a portion of the surface ofthe balloon from one end to the other end of the balloon. The stripe ofdeposited coating material has a width that is typically a fraction ofthe circumference of the balloon. During the spray coating process, theballoon catheter can be rotated as desired, and the step of depositingcoating material can be repeated.

In some aspects of the invention, the spray nozzle is configured toproduce a spray of coating material having a narrow spray pattern. Asused herein, “spray pattern” refers to the shape of the body of coatingmaterial sprayed from the spray nozzle. “Spray” or “sprayed material”refers to the droplets of coating material that are produced from thespray nozzle.

Various types of spray nozzles can be used in association with thecoating apparatus of the invention. In one preferred aspect, the spraynozzle includes a sonicating member, and conduits for solution (coatingmaterial) delivery and air delivery. One exemplary spray nozzle with asonicating member is the MicroFlux XL nozzle sold by SonoTek (Milton,N.Y.). In a sonicating spray coating method, a coating solution isdelivered via a solution delivery line (not shown) to the tip of thespray nozzle. The spray nozzle includes an air delivery/sonicatingmember. At the tip of the nozzle, the solution (coating material) issonicated by the sonicating member, which produces droplets of solution.The droplets are drawn into and carried by the gas stream originating atthe tip of the spray nozzle.

The spray pattern produced by this type of sonicating nozzle isconsiderably narrower than many other spray patterns generated fromtraditional types of spray nozzles. For example, when positioned at adistance of about 0.8 cm from the coating (e.g., balloon) surface, thistype of spray nozzle provides a coating of material on the surface ofthe balloon that has a width of approximately 1-2 mm.

Delivery of the coating material in the form of a spray can be affectedby various operational aspects of the sonicating nozzle. These includethe rate of delivery of the solution, the size of the orifice of thesolution delivery member, the distance of the solution delivery memberfrom the tip of the sonicator/air delivery member, the tip size andconfiguration of the sonicator, the amount of energy provided to thesonicator, the size of the orifice at the outlet of the gas channel, therate of delivery of gas from the gas delivery port (air pressure), andthe type of gas delivered from the spray nozzle.

Other types of spray nozzles can be used in the coating apparatus. Forexample, another type of spray nozzle that can be used in the coatingapparatus is a jet nozzle. Suitable jet nozzles, for example, jetnozzles found in ink jet printers, can be obtained from The Lee Company(Westbrook, Conn.). Various types of ink jet nozzles are contemplated,for example, thermal inkjet nozzles which utilize thermal energy to emitsolution from the nozzle via a pressure wave caused by the thermalexpansion of the solution; electrostatic inkjet nozzles wherein asolution is emitted from the nozzle by electrostatic force;piezoelectric inkjet nozzles in which solution is ejected by means of anoscillator such as a piezoelectric element; and combinations of thesetypes of inkjet nozzles.

In some exemplary modes of practice, the operating conditions forapplication of a spray coating on the surface of the balloon are: about0.03 mL/min of sprayed coating material delivered from the nozzle at apressure of about 2.5 psi, with a balloon rotation speed of about 300RPM.

If the apparatus includes more than one set of rotatable and supportmembers aligned in parallel, the spray nozzle can be movable indirections both parallel (according to arrows 71 and 71′) andperpendicular to the central axes of the rotatable and support members.The spray nozzle can be moved perpendicularly to place the nozzle tip inline with the central axis of the desired rotatable and support members.

The loading or mounting of the balloon catheter in the coating apparatuscan be carried out manually. For example, the balloon catheter can beloaded into the apparatus using the following procedure: First, therotatable member is placed in a position so the central portion isaccessible. For example, if the rotatable member has a split-cylinderconfiguration (such as a split-cylinder configuration that is openedusing a hinge system) the cylinder can be opened to expose its centralportion, which can be a cavity that is coincident with the central axisof the rotatable member. The catheter portion of the balloon cathetercan then be laid in line with the central axis of the rotatable memberand fixed in place. In some modes of practice, the catheter portion isplaced in a cavity (such as one shown in FIGS. 5b and 5c ), which ispreferably of a size and configuration to accommodate the catheterportion. Next, the tip of the balloon catheter is placed in the supportmember so that the distal end of the catheter is secured, yet free torotate. For example, the tip is placed in the center of a grommet oreyelet made of elastomeric material. The tip is secured in the grommetor eyelet by pressure exerted around the periphery of the tip (i.e., thetip tightly fits within the grommet). At that point, and before closingthe split cylinder of the rotatable member, the balloon catheter isstraightened to ensure the catheter portion is taut, and the axis of theballoon catheter is in alignment with the central axis of the rotatablemember. After the balloon catheter has been properly positioned, therotatable member can be closed which fixes the balloon catheter in placefor rotation.

It is contemplated that the steps in the mounting process can bemodified, or the order of the steps changed, while still ultimatelysecuring the balloon catheter for rotation in the apparatus, so the axisof the balloon catheter coincides with the central axis of the device.

Inflation of the balloon portion of the balloon catheter can beperformed prior to the spray coating process. In some modes of practice,inflation of the balloon portion is performed after the balloon catheteris mounted in the device, but before the spray coating process begins.However, the balloon portion can be inflated at any time, such as beforethe balloon catheter is mounted, or even during the coating process.

Referring back to FIG. 1, the proximal end of the catheter typicallyincludes an indeflation port 14. For inflation of the balloon portion12, the indeflation port 14 can be connected to a standard ballooninflation device (e.g., Indeflator™). The balloon portion 12 can then beinflated, which causes expansion of the balloon portion 12 to itspredetermined shape. Preferably, the balloon portion 12 is inflatedusing a gas, such as air. A fully inflated balloon pressure generallyranges from about 6 atm to about 12 atm, with a standard inflatedballoon pressure being about 8 atm. The balloon can be inflated to apredetermined pressure prior to the coating process.

A particular pressure can be chosen so the balloon inflates to apredetermined size for the coating process. During the coating process,the inflated size may be (a) less than the size of the balloon wheninflated at the target site in the body, (b) the same size as theballoon when inflated at the target site in the body, or (c) greaterthan the size as the balloon when inflated at the target site in thebody. In some modes of practice, during the coating process, the size ofthe balloon is the same, or less than the size of the balloon wheninflated at the target site in the body.

In some embodiments of the invention, the coating process is carried outwhen the balloon is inflated to a pressure that is less than the fullyinflated pressure. For example, the balloon has a fully inflatedpressure of about 8 atm, and the coating process is carried out when theballoon is inflated to a pressure of less than about 8 atm.

In one mode of practice, the balloon is inflated to a size that is lessthan the size of the balloon when inflated at the target site in thebody, and then the surface of the balloon is coated. This mode ofpractice can be desirable for forming coatings which are designed tofracture upon inflation to the target size in vivo, wherein portions ofthe fractured coating are released from the balloon surface and providea therapeutic effect to the patient at the target site. That is, theballoon is provided with a coating when the balloon surface has a firstsurface area (and then the coating has this surface area as well), andthen, when placed at a target location in the body, the coating isexpanded to size that provides a second surface area, which is greaterthan the first surface area. As such, this causes the coating tofracture, which in turn promotes delamination of the coating from thesurface of the balloon.

In some modes of practice, the spray nozzle can be moved along thecentral axis while providing a spray of coating material that isdirected at the balloon surface. This results in a portion of theballoon surface being coated and provides a “stripe” of coating materialdeposited along a portion of the length of the balloon. The stripe ofdeposited coating material has a width that is typically a fraction ofthe circumference of the balloon surface. The balloon can be rotated asdesired and the step of depositing coating material on the balloonsurface can be repeated. The step of depositing can be carried out anumber of times to provide a coating having properties as desired. Inmany cases a step of depositing coating material will result in theapplication of coating material over a previously applied area ofcoating material. Deposition of the coating material and rotation of theballoon catheter can be carried out so the coating material driesbetween applications, or partially dries between applications of thecoating material. “Dry” or “dried” refers to the condition of the coatedportion of the balloon surface, wherein the coated portion is not tackyand wherein most of any solvent in the coated portion has evaporatedfrom the balloon surface.

The apparatus and methods of the invention allow for the improved spraycoating of a balloon portion of a balloon catheter. Improvements in thecoating process can be reflected by, for example, in the uniformity ofthe applied coating, the consistency in the amount of applied coating,the protection of other parts of the balloon catheter to obstructdeposition of the coating material, and the increased throughput of thecoating process.

The apparatus and method of the invention can be used to form a coatingon the surface of a balloon portion of a balloon catheter wherein thecoating has one or more desired properties. The invention contemplatesmethods for forming coatings on the balloon surface with any type ortypes of materials that can be delivered from the spray nozzle. Thecoating process is not limited to any particular coating material. Inmany aspects, the coating process involves deposition of a coatingcomposition that includes one or more polymeric material(s) on thesurface of the balloon. Exemplary polymeric materials for coating thesurface of a balloon are described in commonly assigned U.S. patentapplication Ser. No. 12/383,751, filed on Mar. 27, 2009 (Arps et aL).

Typically, the balloon is formed of an elastomeric material, and acoating can be formed on an elastomeric surface to change its surfaceproperties. For example, a coating formed on the surface of the devicecan provide a lubricious surface, which in turn can facilitate movementof the balloon surface when the balloon catheter is inserted in thebody. As another example, the coating can provide a biocompatiblesurface (i.e., a biocompatible surface being one that does not have anadverse biological effect on the tissue which it is in contact with). Inyet other embodiments, the coating method provides a coating on theballoon surface that releases, or facilitates the release of, abioactive agent.

The method can be used to form a coating that includes one or morecoated layers. In a single “coated layer” the materials deposited on thesurface form a film/stratum wherein substantially or entirely the samematerials are present. A single coated layer can also have a certainthickness. In some mode of practice, while the method may involve aplurality of depositions of coating material on the surface of theballoon, if the same coating material is used in the process and theprocess results in a generally uniform material on the surface, thecoating can be considered to have one coated layer.

In some aspects, the coating includes a bioactive agent-releasing layer.A bioactive agent-releasing layer can be adjacent to one or more othercoated layers which can optionally be present in the coating. (Forpurposes of discussion, and also to describe various aspects of theinvention, the coated layers may be described by a “first coated layer”,a “second coated layer”, and, so forth. For example, when describing acoating with two layers, whether a “first layer” is distal or proximalto the surface of the device will be understood in the context of thespecific description of that coating.)

In some aspects, the coating apparatus is used to form a coating on thesurface of a balloon with microparticles embedded in the coating. Amicroparticle-containing coating can be formed to include biodegradablepolymers, biostable polymers, or combinations of both. The coating canalso include a biodegradable polymeric layer which covers themicroparticles.

The apparatus can form a coating wherein the microparticles are theparticulate components that include bioactive agent, and which arereleasable from the elastic surface of the device. The microparticlescan be any three-dimensional particle of size and shape sufficient to beassociated with the surface of the elastic substrate using the coatingmaterials, and then dissociated upon its expansion of the substrate.

Microparticles may have a spherical, or substantially spherical shape,such as those that are formed from synthetic polymeric materials. Inmany aspects, the elastic portion of the device is associated withspherical or substantially spherical microparticles. However,microparticles associated with a balloon surface can have noticeablynon-spherical shapes or irregular shapes (for example, when examined bymicroscopy). For example, microparticles can have curved surfaces, flatsurfaces, or combinations thereof. If desired, the expandable elasticportion can be associated with a plurality of microparticles of acombination of different sizes and/or shapes.

In many aspects, microparticles associated with the expandable elasticportion using the apparatus and/or method of the invention have anaverage diameter (“dn”, number average) that is less than about 50 μm.Also, in many aspects, the microparticles can have an average diameterof about 100 nm or larger. For example, the microparticles associatedwith the expandable elastic portion can have an average diameter in therange of about 100 nm to about 50 μm, about 150 nm to about 25 μm, about200 nm to about 20 μm, or about 0.3 μm to about 10 μm.

Depending on the manner by which the microparticles are associated withthe elastic portion, it can be desirable to use microparticles within aparticular size range. For example, when the microparticles areimmobilized in a coating on the surface of the elastic portion, it isgenerally desirable to utilize microparticles having an average diameterthat is smaller than the thickness of the coating.

In the least, the microparticles that are associated with the expandableelastic substrate using the apparatus and/or method of the inventioninclude a bioactive agent. Therefore, in some embodiments, themicroparticles can be formed completely or substantially of a selectedbioactive agent for treatment or prevention of a condition. In otherembodiments, the microparticles can be formed from a combination ofbioactive agents (e.g., two or more different bioactive agents). Inother embodiments, the microparticles can be formed from a bioactiveagent and another component that is not intended to provide atherapeutic effect to the subject, such as a polymer that can modulatethe release of the bioactive agent from the microparticles. In otherembodiments the microparticles include two or more components, such astwo or more polymers that modulate the release of the bioactive agentfrom the microparticle.

Components of the microparticle can be in mixture with one another in aportion of, or all of, the microparticle. Alternatively, the componentscan be entirely or substantially separated from one another in themicroparticle. For example, the microparticle can be formed comprising asubstantially homogenous mixture of a bioactive agent and arelease-modulating polymer. As another example, the microparticle can beformed comprising a bioactive agent core and a release-modulatingpolymer shell around the core.

The coating apparatus and/or method of the invention can be used toprepare microparticle-containing coatings as described in commonlyassigned U.S. patent application Ser. No. 12/383,751, filed on Mar. 27,2009 (Arps et al.).

The term “bioactive agent,” refers to an inorganic or organic molecule,which can be synthetic or natural, that causes a biological effect whenadministered in vivo to an animal, including but not limited to birdsand mammals, including humans. A partial list of bioactive agents isprovided below. One may choose any one of the bioactive agents to beincluded in a microparticle set alone, or in combination with any otherbioactive agent. A comprehensive listing of bioactive agents, inaddition to information of the water solubility of the bioactive agents,can be found in The Merck Index, Thirteenth Edition, Merck & Co. (2001).

The microparticles, which are released from the elastic substrates, canbe used to deliver bioactive agents falling within one or more of thefollowing classes, which include, but are not limited to, ACEinhibitors, actin inhibitors, analgesics, anesthetics,anti-hypertensives, anti polymerases, antisecretory agents, antibiotics,anti-cancer substances, anti-cholinergics, anti-coagulants,anti-convulsants, anti-depressants, anti-emetics, antifungals,anti-glaucoma solutes, antihistamines, antihypertensive agents,anti-inflammatory agents (such as NSAIDs), anti metabolites,antimitotics, antioxidizing agents, anti-parasite and/or anti-Parkinsonsubstances, antiproliferatives (including antiangiogenesis agents),anti-protozoal solutes, anti-psychotic substances, anti-pyretics,antiseptics, anti-spasmodics, antiviral agents, calcium channelblockers, cell response modifiers, chelators, chemotherapeutic agents,dopamine agonists, extracellular matrix components, fibrinolytic agents,free radical scavengers, growth hormone antagonists, hypnotics,immunosuppressive agents, immunotoxins, inhibitors of surfaceglycoprotein receptors, microtubule inhibitors, miotics, musclecontractants, muscle relaxants, neurotoxins, neurotransmitters,polynucleotides and derivatives thereof, opioids, prostaglandins,remodeling inhibitors, statins, steroids, thrombolytic agents,tranquilizers, vasodilators, and vasospasm inhibitors.

In some aspects the microparticles comprise an antiproliferative agent.The antiproliferative agent can be an anti-angiogenesis agent.

In some aspects the microparticles comprise an anti-inflammatory agent.

In some aspects the microparticles comprise a cell response modifier.

In some aspects the microparticles comprise an anti-thrombotic agent.

In some aspects the microparticles comprise an immunosuppressive agent.

What is claimed is:
 1. An apparatus for coating a balloon catheter, the apparatus comprising: (a) a rotatable member comprising an elongated cylinder split along its length from proximal to distal ends, the rotatable member having a distal end and a proximal end, a central axis about which the rotatable member can be rotated and which is configured to accommodate and fix a catheter body of a balloon catheter having a catheter axis so the central axis is aligned with the catheter axis and so the catheter body can be rotated about its catheter axis from a catheter body proximal end to a catheter body distal end, wherein the rotatable member has a length in the range of 50 cm to 200 cm; (b) a support member comprising a grommet, which is aligned with the central axis of the rotatable member, which is configured to hold and allow rotation of a distal tip of the catheter body when the catheter body of the balloon catheter is fixed and rotated in the rotatable member, and wherein the distal end of the rotatable member is separated from the support member by a gap, wherein the rotatable member and the support member are arranged to support the balloon catheter so its catheter axis is in a substantially horizontal position; (c) a drive mechanism comprising a motor which causes rotation of at least one of the rotatable member and the support member; and (d) a coating nozzle for delivering coating material in the gap between the distal end of the rotatable member and the support member.
 2. The apparatus of claim 1 further comprising a balloon inflation device.
 3. The apparatus of claim 1 wherein the drive mechanism is attached to the proximal end of the rotatable member.
 4. The apparatus of claim 1 wherein the support member comprises a friction-reducing material .
 5. The apparatus of claim 1 wherein the rotatable member and the support member are independently mounted on a common housing.
 6. The apparatus of claim 1 wherein the rotatable member comprises two half cylinders hinged along one side of the rotatable member.
 7. The apparatus of claim 1 wherein the grommet comprises an orifice into which the distal tip of the catheter body is placed, the orifice having a diameter in the range of about 0.1 cm to about 2.0 cm.
 8. The apparatus of claim 1 wherein the support member is not rotatable along with the distal tip of the catheter body.
 9. The apparatus of claim 1 wherein the coating nozzle comprises a spray nozzle.
 10. The apparatus of claim 9 wherein the spray nozzle comprises a sonicating member. 